Amlodipine and its salts are long acting calcium channel blockers and are useful for the treatment of cardiovascular disorders. Racemic Amlodipine is currently being used as its besylate in the treatment of hypertension and angina. The preparation of racemic compound is described in European patent 0089167. Amlodipine is racemic compound and has chiral center at 4 position of the dihydropyridine ring.
It has also been reported that the R(+) isomer is a potent inhibitor of smooth muscle cell migration (PCT/EP-94/02697). The S(−) isomer is having calcium channel blocker activity while the R(+) isomers has little or no calcium channel blocking activity.
Prior art for the preparation of R and S enantiomers of amlodipine are a) resolution of amlodipine azide ester with optically active 2-methoxy-2-phenylethanol (J. Med. Chem., 29, 1696, 1986. J. E. Arrowsmith, S. F. Campbell, P. E. Cross, J. K Stabs, R. A., Burges and EP Appl. 0331315A) or b) resolution of Amlodipine base with optically active camphanic acid [J. Med. Chem., 35, 3341, 1992, S. Goldman, J. Stoltefuss and L. Born) or c) resolution of RS.-amlodipine base to R(+) and S(−) isomer with L or D tartaric acid respectively in organic solvent DMSO {Peter L., Spargo U.S. Pat. No. 6,046,338; (2000), PCT 95/25722 (1995)] which indicate the use of both tartaric acids is essential.
The Disadvantages:
The main disadvantages of the prior art are:
    1. The use of unnatural tartaric acid for the separation of S(−) amlodipine    2. The use of costlier camphanic acid or 2-methoxy-2-phenylethanol as a resolving agents.